title: Results from a dose-response study using 3,3'-diindolylmethane in the K14-HPV16 transgenic mouse model: cervical histology.
abstract: The human papilloma virus is the major cause of cervical cancer. Viral infection initiates cervical intraepithelial neoplasia, which progresses through several stages to cervical cancer. The objective of this study is to identify the minimum effective dose of diindolylmethane that prevents the progression from cervical dysplasia to carcinoma in situ. We document cervical histology in K14-HPV16 mice receiving different doses of diindolylmethane. Urinary diindolylmethane concentrations are reported. Diindolylmethane could enhance the efficacy of human papilloma virus vaccines, creating a new therapeutic use for these vaccines in women already infected with the virus. Five doses (0-2,500 ppm) of diindolylmethane were incorporated into each mouse diet. The reproductive tract was serially sectioned and urine was obtained for analysis of urinary diindolylmethane. The results indicate that 62% of mice receiving 1,000 ppm diindolylmethane remained dysplasia-free after 20 weeks compared with 16% of mice receiving no diindolylmethane and 18% receiving 500 ppm; 1,000 ppm of 3,3'-diindolylmethane in the diet completely suppressed the development of cervical cancer. Urinary diindolylmethane levels increased significantly as diindolylmethane in food increased. These findings imply usefulness for diindolylmethane in the search to prevent cervical cancer when used in combination with prophylactic or therapeutic vaccines.
authors.affiliation: The David and Alice Institute for Research, Hackensack University Medical Center, New Jersey 07601, USA. dsepkovic@humed.com
authors.forename: Daniel W
authors.initials: DW
authors.lastname: Sepkovic
authors.forename: Johann
authors.initials: J
authors.lastname: Stein
authors.forename: Antoine D
authors.initials: AD
authors.lastname: Carlisle
authors.forename: H Barbara
authors.initials: HB
authors.lastname: Ksieski
authors.forename: Karen
authors.initials: K
authors.lastname: Auborn
authors.forename: Laura
authors.initials: L
authors.lastname: Raucci
authors.forename: Themba
authors.initials: T
authors.lastname: Nyirenda
authors.forename: H Leon
authors.initials: HL
authors.lastname: Bradlow
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000008:administration & dosage* / Q000652:urine; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005260:Female; D006801:Humans; D007211:Indoles / Q000008:administration & dosage* / Q000652:urine; D051379:Mice; D008822:Mice, Transgenic; D027383:Papillomaviridae / Q000145:classification / Q000302:isolation & purification; D030361:Papillomavirus Infections / Q000473:pathology / Q000517:prevention & control* / Q000821:virology; D053918:Papillomavirus Vaccines / Q000008:administration & dosage; D002578:Uterine Cervical Dysplasia / Q000473:pathology / Q000517:prevention & control* / Q000821:virology; D002583:Uterine Cervical Neoplasms / Q000473:pathology / Q000517:prevention & control* / Q000821:virology
chemical_list: D016588:Anticarcinogenic Agents; D007211:Indoles; D053918:Papillomavirus Vaccines; C016392:3,3'-diindolylmethane